Low-Concentration Norepinephrine Infusion for Major Surgery: A Safety and Feasibility Pilot Randomized Controlled Trial.

ABSTRACT

BACKGROUND: Prevention of hypotension during the intra- and postoperative period is an important goal. Peripheral administration of low-concentration norepinephrine may be a safe and effective strategy to reduce the risk of hypotension. METHODS: We conducted a 2-center, randomized pilot feasibility trial, with a target of 60 adult patients undergoing major noncardiac surgery. We randomized patients to receive a peripheral low-concentration (10 µg/mL) norepinephrine or placebo (saline 0.9%) infusion. The study drug infusion was titrated to achieve a minimum systolic blood pressure target, preselected within 10% of baseline value and within the range limit 100 to 120 mm Hg during surgery and for up to 4 or 24 hours postoperatively. RESULTS: We achieved a high consent rate (84%), successful study drug administration throughout surgery (98% of patients) and absence of unblinding. There were no important study drug-related adverse events. The average intraoperative systolic blood pressure was 120 ± 12.6 mm Hg in the norepinephrine group and 115 ± 14.9 mm Hg in the placebo group. The mean difference between the intraoperative systolic blood pressure achieved less the preselected minimum systolic blood pressure target was 10.0 ± 12.7 mm Hg in the norepinephrine group and 2.9 ± 14.7 mm Hg in the placebo group; difference in means, 7.1 (95% confidence interval, 0.2-14.0) mm Hg. CONCLUSIONS: A future large trial evaluating the effectiveness and safety of peripheral administration of low-concentration norepinephrine during the perioperative period is feasible, and likely to achieve a minimum systolic blood pressure threshold.